Clinical Trials Register

Summary
EudraCT Number:	2017-001356-59
Sponsor's Protocol Code Number:	205847
National Competent Authority:	Czechia - SUKL
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2017-08-02
Trial results	View results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

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A. Protocol Information

A.1

Member State Concerned

Czechia - SUKL

A.2

EudraCT number

2017-001356-59

A.3

Full title of the trial

A phase IV, open-label, single-center study to evaluate long term immunogenicity up to 15 years after the first booster immunization with Encepur Adults (Polygeline-free Tick-borne Encephalitis vaccine for adults) in adults who received 1 of 3 different primary vaccination schedules.

Otevřená monocentrická klinická studie fáze IV hodnotící dlouhodobou imunogenitu po dobu až 15 let po prvním přeočkování vakcínou Encepur pro dospělé (proti klíšťové encefalitidě pro dospělé bez obsahu polygelinu) u dospělých očkovaných jedním ze 3 různých základních očkovacích schémat.

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

Long term immunogenicity up to 15 years after the first booster immunization with GSK Biologicals’Encepur Adults in adults who received 1 of 3 different primary vaccination schedules.

Hodnocení dlouhodobé imunogenity po dobu až 15 let po prvním přeočkování vakcínou Encepur pro dospělé společnosti GSK Biologicals u dospělých očkovaných jedním ze 3 různých základních očkovacích schémat.

A.3.2

Name or abbreviated title of the trial where available

TBEV POLYGELINE FREE-025 EXT:021

A.4.1

Sponsor's protocol code number

205847

A.7

Trial is part of a Paediatric Investigation Plan

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	GlaxoSmithKline Biologicals
B.1.3.4	Country	Belgium
B.3.1 and B.3.2	Status of the sponsor	Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	GlaxoSmithKline Biologicals
B.4.2	Country	Belgium
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	GlaxoSmithKline Biologicals
B.5.2	Functional name of contact point	Clinical Disclosure Advisor
B.5.3	Address:
B.5.3.1	Street Address	Rue de l’Institut, 89
B.5.3.2	Town/ city	Rixensart
B.5.3.3	Post code	1330
B.5.3.4	Country	Belgium
B.5.4	Telephone number	442089904466
B.5.6	E-mail	GSKClinicalSupportHD@gsk.com

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.1.1.1	Trade name	ENCEPUR ADULTS (Encepur Erwachene)
D.2.1.1.2	Name of the Marketing Authorisation holder	GSK Vaccines GmbH
D.2.1.2	Country which granted the Marketing Authorisation	Germany
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.4	Pharmaceutical form	Suspension for injection in pre-filled syringe
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intramuscular use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	-
D.3.9.3	Other descriptive name	TICK-BORNE ENCEPHALITIS VIRUS (INACTIVATED), STRAIN K23
D.3.9.4	EV Substance Code	SUB29400
D.3.10	Strength
D.3.10.1	Concentration unit	µg microgram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	1.5
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	No
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	Yes
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	Yes
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No

D.8 Information on Placebo

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Healthy volunteers (Active immunization in individuals from 12 years of age against tick-borne encephalitis (TBE) virus. The vaccination is intended for residents or travellers in TBE-endemic areas, according to national recommendations).

E.1.1.1

Medical condition in easily understood language

Inflammation of the brain or the membranes surrounding the brain and spinal cord.

E.1.1.2

Therapeutic area

Diseases [C] - Virus Diseases [C02]

MedDRA Classification

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

To evaluate the persistence of antibody response to a booster dose of Encepur Adults vaccine starting ≥ 11 years after the first booster administration and to continue following subjects up to 15 years after first booster administration.

E.2.2

Secondary objectives of the trial

To evaluate the immune response at 21 days after booster dose (boostability) in subjects with an NT titre below 10.
To evaluate the safety of a booster dose with regard to SAEs collected after vaccination until study end.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

Inclusion criteria for all subjects:
-Subjects who, in the opinion of the investigator, can and will comply with the requirements of the protocol.
-Written informed consent obtained from the subject prior to performance of any study specific procedure.
-Subjects who have participated in study V48P7E2 (NCT01562444) and who received in the parent V48P7 study one of the following schedules: rapid, conventional, or accelerated conventional and a booster vaccination in study V48P7E1 (NCT00387634) or before study V48P7E1 (NCT00387634) (only rapid schedule)

Additional inclusion criteria for subjects who will need a second booster dose:
-Healthy subjects as established by medical history and clinical examination before entering into the study.
-Female subjects of non-childbearing potential may be enrolled in the study. Non-childbearing potential is defined as pre-menarche, current bilateral tubal ligation or occlusion, hysterectomy, bilateral ovariectomy or post-menopause.
- Female subjects of childbearing potential can receive the booster vaccine in the study, if the subject: has practiced adequate contraception for 30 days prior to vaccination, and has a negative pregnancy test on the day of vaccination, and has agreed to continue adequate contraception for 2 months after booster administration.

E.4

Principal exclusion criteria

Each subject must not be:
- Unwilling or unable to give written informed consent to participate in the study.
- Perceived to be unreliable or unavailable to complete the study.

Each subject must not have:
-Clinical conditions representing a contraindication to blood draws.
-Any other clinical condition that, in the opinion of the investigator, might interfere with the results of the study or pose additional risk to the subject due to participation in the study.
-Received an investigational or non-registered medicinal product within 30 days prior to informed consent.
-Concurrently participating in another clinical study, at any time during the study period, in which the subject has been or will be exposed to an investigational or a non-investigational vaccine/product).
-Levels of NT<10 in V48P7E2 (NCT01562444) study.
-Previous vaccination against TBE or other Flavivirus diseases with other TBE and Flavivirus vaccines (e.g. Yellow fever vaccine, Dengue fever vaccine, Japanese encephalitis vaccine) before, during and after completion of the V48P7E2 (NCT01562444) and before starting TBEV POLYGELINE FREE-025 EXT 21 study.
-Primary immunization with TBE vaccine in the parent study V48P7 according to the modified conventional (MC) schedule.
-History of confirmed TBE infection.
-Known exposure to other Flaviviruses.

Each subject who will receive the second booster vaccination in this study additionally to the exclusion criteria above must not have:
-Hypersensitivity, including allergy, to any component of vaccines, medicinal products or medical equipment whose use is foreseen in this study.
-Clinical conditions representing a contraindication to intramuscular vaccination.
-Progressive, unstable or uncontrolled clinical conditions.
-Abnormal function of the immune system resulting from: Clinical conditions. Systemic administration of corticosteroids for more than 14 consecutive days within 90 days prior to informed consent. This will mean prednisone ≥20 mg/day (for adult subjects) or equivalent. Inhaled and topical steroids are allowed. Administration of antineoplastic and immuno-modulating agents or radiotherapy within 90 days prior to vaccination.
-Received immunoglobulins or any blood products within 180 days prior to vaccination.
-Administration of long-acting immune-modifying drugs at any time during the study period.
-Acute disease and/or fever at the day of booster vaccination.
-Expected general decrease in immune response.
-Organic brain disturbances, including seizure disorders.
-Progressive neurological disorders.
-Suffered febrile or afebrile convulsions.
-Serious chronic illness.
-History of any reaction or hypersensitivity likely to be exacerbated by any component of the vaccine or chemically related substances.
-Individuals who received any other vaccines within 14 days (for inactivated vaccines) or 28 days (for live vaccines) prior to vaccination in this study or who are planning to receive any vaccine within 28 days from the study vaccines.
-Pregnant.

E.5 End points

E.5.1

Primary end point(s)

Percentages of subjects with detectable TBE Neutralizing Antibody Titres ≥ 2 and ≥ 10 as measured by GSK Bio-logicals’ NT.

Geometric Mean Antibody Titres as measured by GSK Biologicals’ NT calculated for each of the different schedule groups.

This endpoint will be summarized according to the immunization schedule received in the V48P7E1 (NCT00387634) study and further detailed by the following age subgroups: 25 to 49 years, ≥ 50 years and ≥ 60 years.

E.5.1.1

Timepoint(s) of evaluation of this end point

Year 11, Year 12, Year 13, Year 14, Year 15

E.5.2

Secondary end point(s)

Percentages of subjects with detectable TBE Neutralizing Antibody Titres ≥ 2 and ≥ 10 as measured by GSK Bio-logicals’ NT, overall and by study group.

Geometric Mean Antibody Titres and Geometric Mean Ratios (GMRs) blood draw after/before booster as meas-ured by GSK Biologicals’ NT, overall and by study group.

Thorough description of NT waning in order to complement the analysis of persistence. To complement the analysis of persistence, a thorough description of NT waning from year 1 after the first booster dose up to 15 years will be presented for the set of subjects completing the entire 15-year follow-up with no protocol deviations, including those receiving a second booster dose; for whom, a constant value of NT = 1 from the post booster visit will be used in the analysis

This endpoint will be summarized according to the primary immunization schedule received in the parent study (V48P7).

Incidence of serious adverse events (SAEs).
The safety endpoint for subjects who will need a second booster vaccination will be based on SAEs collection after the second booster dose.
SAEs are defined as any untoward medical occurrence that results in death, is life- threatening, requires hospitalisation or prolongation of existing hospitalisation, results in disabil-ity/incapacity or is a congenital anomaly/birth defect in the offspring of a study subject.

E.5.2.1

Timepoint(s) of evaluation of this end point

At 21 days after the booster vaccination.

For SAEs: At 1 month after vaccination. Based on the timing of the booster dose, at Years 11.5 (Visit 23.1), 12.5 (Visit 24.1), 13.5 (Visit 25.1), or 14.5 (Visit 26.1) or from year 15.5 (Visit 27.1) until 21 days after year 15.5 (Visit 27.2)

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

Yes

E.6.3

Therapy

E.6.4

Safety

Yes

E.6.5

Efficacy

E.6.6

Pharmacokinetic

E.6.7

Pharmacodynamic

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

Yes

E.6.13.1

Other scope of the trial description

Persistence - Immunogenicity

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

E.7.3

Therapeutic confirmatory (Phase III)

E.7.4

Therapeutic use (Phase IV)

Yes

E.8 Design of the trial

E.8.1

Controlled

E.8.1.1

Randomised

E.8.1.2

Open

Yes

E.8.1.3

Single blind

E.8.1.4

Double blind

E.8.1.5

Parallel group

E.8.1.6

Cross over

E.8.1.7

Other

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

E.8.2.2

Placebo

E.8.2.3

Other

E.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

Yes

E.8.4

The trial involves multiple sites in the Member State concerned

E.8.5

The trial involves multiple Member States

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.7

Trial has a data monitoring committee

E.8.8

Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial

Last testing results released of samples collected at Visit 27 or
Visit 27.2

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

F.1.1.1

In Utero

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

F.1.1.3

Newborns (0-27 days)

F.1.1.4

Infants and toddlers (28 days-23 months)

F.1.1.5

Children (2-11years)

F.1.1.6

Adolescents (12-17 years)

F.1.2

Adults (18-64 years)

Yes

F.1.2.1

Number of subjects for this age range:

163

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

Yes

F.3.2

Patients

F.3.3

Specific vulnerable populations

Yes

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

Yes

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

F.3.3.6

Subjects incapable of giving consent personally

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

200

F.5

Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)

None.

G. Investigator Networks to be involved in the Trial

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2017-09-15

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2017-09-07

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2022-03-08

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